Polyclonal B cell activation by B cell differentiation factor B151-TRF2. I. Involvement of self-Ia recognition process mediated by B cells.
Polyclonal B cell activation by B cell differentiation factor B151-TRF2. I. Involvement of self-Ia recognition process mediated by B cells.
复制标题
B 细胞分化因子 B151-TRF2 激活多克隆 B 细胞。
作者：
S. Ono;Y. Takahama;T. Hamaoka
本研究检测了 Ia 抗原在 B 细胞分化因子 B151-TRF2 诱导的多克隆 B 细胞激活中的功能作用。 B151-TRF2 的多克隆 IgM PFC 反应被 II 类 MHC 抗原（Ia 抗原）特异性单克隆抗体抑制，但不被 I 类 MHC 抗原抑制。抗Ia抗体的这种抑制是单倍型特异性的，并且在T细胞和辅助细胞都不存在的情况下观察到。此外，抗Ia抗体诱导的B151-TRF2反应的抑制并不是由于B151-TRF2与相应B细胞受体的结合的阻断所致。一系列动力学研究表明，一些 Ia 介导的细胞激活过程发生在静息 B 细胞对 B151-TRF2 产生反应之前。因此，B151-TRF2 介导的 B 细胞反应由至少两个不同的阶段组成。早期阶段是Ia依赖性但B151-TRF2独立的过程，而晚期是Ia独立但B151-TRF2依赖性的过程。为了进一步表征 Ia 抗原对 B 细胞的功能作用，使用表面共显性表达两种亲本 Ia 抗原的 F1 B 细胞进行了额外的实验。有趣的是，观察到抗亲本 Ia 抗体对 B151-TRF2 介导的 F1 B 细胞反应的抑制程度最多是亲本 B 细胞的一半，这表明 F1 B 细胞可能被分成两个亚群，对各自的亲本 Ia 抗原具有限制性特异性。为了检验这种可能性，根据 (B10 X B10.BR)F1 B 细胞与任一亲本 B 细胞单层结合的能力将 (B10 X B10.BR)F1 B 细胞分为贴壁细胞群和非贴壁细胞群，并评估了抗 Ia 抗体对其对 B151-TRF2 反应的抑制特异性。结果发现，粘附于 B10 B 细胞单层或 B10.BR B 细胞单层的 (B10 X B10.BR)F1 B 细胞的反应几乎完全被抗 I-Ab 和抗 I-Ak 抗体抑制，而非粘附细胞的反应则分别被抗 I-Ak 和抗 I-Ab 抗体选择性抑制。这些发现被解释为表明 B151-TRF2 反应性 F1 B 细胞由至少两个对任一亲本 Ia 抗原具有限制性特异性的亚群组成。（摘要截断为 400 字）
The present study examined the functional role of Ia antigens on B cells in polyclonal B cell activation induced by a B cell differentiation factor, B151-TRF2. The polyclonal IgM PFC responses by B151-TRF2 were inhibited by monoclonal antibodies specific for class II MHC antigens (Ia antigens) but not class I MHC antigens. Such inhibition by anti-Ia antibodies was haplotype-specific and was observed in the absence of both T cells and accessory cells. Moreover, the anti-Ia antibody-induced inhibition of the B151-TRF2 responses was not due to the blocking of binding of B151-TRF2 to the corresponding B cell receptor. A series of kinetic studies revealed that some Ia-mediated cellular activation process occurs before the resting B cells become responsive to B151-TRF2. Thus, the B151-TRF2-mediated B cell responses consist of at least two distinct phases. The early phase is an Ia-dependent but B151-TRF2-independent process, whereas the late phase is an Ia-independent but B151-TRF2-dependent process. To further characterize the functional role of Ia antigens on B cells, an additional experiment was carried out by using F1 B cells which co-dominantly express both parental Ia antigens on the surface. Interestingly, it was observed that the degree of inhibition of the B151-TRF2-mediated responses of F1 B cells by anti-parental Ia antibody was, at best, one-half that of the parental B cells, suggesting that F1 B cells may be separated into two subpopulations with the restriction specificity for the respective parental Ia antigens. To examine this possibility, (B10 X B10.BR)F1 B cells were separated into adherent and nonadherent cell populations by their ability to bind to either one of the parental B cell monolayers, and the specificity of inhibition of their responses to B151-TRF2 by anti-Ia antibodies was assessed. It was found that the responses of (B10 X B10.BR)F1 B cells adherent to the B10 B cell monolayer or the B10.BR B cell monolayer were almost completely inhibited by anti-I-Ab and anti-I-Ak antibodies, whereas those of nonadherent cells were now selectively inhibited by anti-I-Ak and anti-I-Ab antibodies, respectively. These findings are interpreted as indicating that the B151-TRF2-responsive F1 B cells consist of at least two subpopulations with the restriction specificity for either one of the parental Ia antigens.(ABSTRACT TRUNCATED AT 400 WORDS)